Nikhil S. Malvankar
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Biography
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Research Summary
Single-cell Imaging and Control of Microbial Functions using Protein Nanowires “Life is nothing but an electron looking for a place to rest.” - Nobel Laureate A. Szent-Gyorgi
Electron transfer is central to all life processes. To avoid damage, organisms have evolved strategies to eliminate the surplus of electrons created by metabolism, using oxygen-like electron acceptors, which act as electron sinks. However, microbes that live in areas with no oxygen, such as those that reside in the deep ocean, in soil, or in the human body, have evolved strategies to export electrons to extracellular acceptors, such as minerals and other bacteria. Geobacter uses long, thin, conductive filaments called “nanowires” to export electrons. Nanowires are fundamental to the global environment & are also required in some infections.
Geobacter nanowires have intrigued the scientific community since they were first identified in 2002. Until recently, nanowires were thought to be pili. However, our lab’s recent work demonstrates that pili structure is inconsistent with electron transfer, whereas cytochrome filaments could transfer electrons through a continuous chain of heme groups. We are now testing hypotheses that (i) these cytochromes are the nanowires (Cell 2019, Nature Chem.Bio. 2020, Nature Micro. 2023), and that (ii) pili function akin to a piston to secrete cytochrome across the outer membrane (Nature 2021). We aim to determine nanowires' structure, assembly, and electron transfer mechanism and evaluate their role in respiration, communication, and pathogenesis.
Extensive Research Description
By combining experimental and computations, we are addressing three key questions:
- How do microbes build & use nanowires?
- How are electrons transferred from the bacterial cytoplasm to surface-displayed nanowires?
- Can nanowire conductivity be tuned via light, pressure, electric- & magnetic-fields to control bacteria?
Using what we learn from these studies, our long-term vision is to monitor and control the growth of microbes residing in the deep ocean, in soil, or in the human body to use nanowires in four areas:
1) Fundamental studies to elucidate how diverse microbes assemble and use various nanowires.
2) Repair soil and marine environmental health using microbial nanowire-mediated electron exchange.
3) Restore rhizosphere health by targeting nanowire-mediated microbe-plant interactions; and
4) Restore human health by controlling the growth and colonization of clinically important microbes.
Towards this vision, in the shorter term (next 3-5 years), we plan to make inroads in the:
1) In situ structural and functional imaging of metabolism within microbial communities using our electron imaging (Nature Nano.) combined with cryo-electron microscopy & tomography (with Jun Liu)
2) Understanding conductivity mechanisms employed by protein nanowires. We are determining how nanowires move electrons, ions, spins, and excitons at unprecedented ultrafast (< 200 fs) rates ( Nature Comm. 2022) and over centimeter distances. We have found a novel electron escape route in proteins to avoid oxidative damage (PNAS 2021) and how cooling speeds up electrons (Science Adv. 2022).
3) Control bacterial metabolism to develop Antibiotics: Disrupting electron export to inhibit growth and adhesion of pathogens and Probiotics: Accelerating electron export to promote growth of commensals.
Small wires, big opportunities. Protein nanowires provide unprecedented ability to control microbial function and design custom microbial communities. We are establishing a fundamentally new class of electron-conducting protein nanowires and electrogenetics, making it possible to electronically control any microbe as electronic analogs of GFP and optogenetics to monitor and control the growth, communication, and colonization of microbes deep inside the Earth and in human cells.
Projects involve structural studies, genetically engineering nanowire conductivity, nanoscale electron transfer measurements in nanowires and living biofilms, spectroelectrochemistry, and building and experimentally testing computational models through ongoing collaborations with Batista and Brudvig (Yale, Chem.), Lisa Craig (Canada), Olivera Francetic (France), and Carlos Salgueiro (Portugal).
We have several interdisciplinary projects embedded in these larger goals that would be great rotation projects. They provide training in a variety of biophysical, molecular biology, and biochemical techniques and are likely to yield positive results/publications within the rotation. Please chat to match your interests with training opportunities. Projects are experimentally or computationally-oriented, with possibilities of combining both. No prior background is necessary.
Please chat with PI or one of laboratory members to match your interests with our training opportunities. Rotation projects are experimentally or computationally-oriented with the possibility of combining both, and no prior background in a specific discipline is necessary.
Join our lab meetings in person or via Zoom on Wednesday at 11 AM (with international collaborators) and 12:30 PM (group). We can adapt our lab meeting schedule to accommodate your class schedule.
Coauthors
Research Interests
Bacteria, Anaerobic; Bacterial Adhesion; Bacterial Infections; Biophysics; Chemistry, Physical; Electron Transport; Environmental Microbiology; Microscopy, Atomic Force; Nanotechnology
Public Health Interests
Environmental Health; Infectious Diseases; Respiratory Disease/Infections
Research Images
Selected Publications
- Borg extrachromosomal elements of methane-oxidizing archaea have conserved and expressed genetic repertoiresSchoelmerich M, Ly L, West-Roberts J, Shi L, Shen C, Malvankar N, Taib N, Gribaldo S, Woodcroft B, Schadt C, Al-Shayeb B, Dai X, Mozsary C, Hickey S, He C, Beaulaurier J, Juul S, Sachdeva R, Banfield J. Borg extrachromosomal elements of methane-oxidizing archaea have conserved and expressed genetic repertoires. Nature Communications 2024, 15: 5414. PMID: 38926353, PMCID: PMC11208441, DOI: 10.1038/s41467-024-49548-8.
- Author Correction: Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivityGu Y, Guberman-Pfeffer M, Srikanth V, Shen C, Giska F, Gupta K, Londer Y, Samatey F, Batista V, Malvankar N. Author Correction: Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivity. Nature Microbiology 2024, 1-1. PMID: 38684912, DOI: 10.1038/s41564-024-01702-0.
- Widespread extracellular electron transfer pathways for charging microbial cytochrome OmcS nanowires via periplasmic cytochromes PpcABCDEPortela P, Shipps C, Shen C, Srikanth V, Salgueiro C, Malvankar N. Widespread extracellular electron transfer pathways for charging microbial cytochrome OmcS nanowires via periplasmic cytochromes PpcABCDE. Nature Communications 2024, 15: 2434. PMID: 38509081, PMCID: PMC10954620, DOI: 10.1038/s41467-024-46192-0.
- Outer membrane vesicles and the outer membrane protein OmpU govern Vibrio cholerae biofilm matrix assemblyPotapova A, Garvey W, Dahl P, Guo S, Chang Y, Schwechheimer C, Trebino M, Floyd K, Phinney B, Liu J, Malvankar N, Yildiz F. Outer membrane vesicles and the outer membrane protein OmpU govern Vibrio cholerae biofilm matrix assembly. MBio 2024, 15: e03304-23. PMID: 38206049, PMCID: PMC10865864, DOI: 10.1128/mbio.03304-23.
- 195 Aberrant Brain Biomechanics Initiates Ventricular Dilation in a Genetic Subtype of Congenital HydrocephalusPhan D, Dahl P, Koundal S, Pedram M, Deniz E, Benveniste H, Malvankar N, Kahle K. 195 Aberrant Brain Biomechanics Initiates Ventricular Dilation in a Genetic Subtype of Congenital Hydrocephalus. Neurosurgery 2023, 69: 32-32. DOI: 10.1227/neu.0000000000002375_195.
- Author Correction: Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunctionXing H, Huang Y, Kunkemoeller B, Dahl P, Muraleetharan O, Malvankar N, Murrell M, Kyriakides T. Author Correction: Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction. Scientific Reports 2023, 13: 4253. PMID: 36918662, PMCID: PMC10015071, DOI: 10.1038/s41598-023-31191-w.
- Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivityGu Y, Guberman-Pfeffer M, Srikanth V, Shen C, Giska F, Gupta K, Londer Y, Samatey F, Batista V, Malvankar N. Structure of Geobacter cytochrome OmcZ identifies mechanism of nanowire assembly and conductivity. Nature Microbiology 2023, 8: 284-298. PMID: 36732469, PMCID: PMC9999484, DOI: 10.1038/s41564-022-01315-5.
- Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunctionXing H, Huang Y, Kunkemoeller B, Dahl P, Muraleetharan O, Malvankar N, Murrell M, Kyriakides T. Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction. Scientific Reports 2022, 12: 22474. PMID: 36577792, PMCID: PMC9797577, DOI: 10.1038/s41598-022-26337-1.
- Microbial biofilms as living photoconductors due to ultrafast electron transfer in cytochrome OmcS nanowiresNeu J, Shipps CC, Guberman-Pfeffer MJ, Shen C, Srikanth V, Spies JA, Kirchhofer ND, Yalcin SE, Brudvig GW, Batista VS, Malvankar NS. Microbial biofilms as living photoconductors due to ultrafast electron transfer in cytochrome OmcS nanowires. Nature Communications 2022, 13: 5150. PMID: 36071037, PMCID: PMC9452534, DOI: 10.1038/s41467-022-32659-5.
- A 300-fold conductivity increase in microbial cytochrome nanowires due to temperature-induced restructuring of hydrogen bonding networksDahl PJ, Yi SM, Gu Y, Acharya A, Shipps C, Neu J, O’Brien J, Morzan UN, Chaudhuri S, Guberman-Pfeffer MJ, Vu D, Yalcin SE, Batista VS, Malvankar NS. A 300-fold conductivity increase in microbial cytochrome nanowires due to temperature-induced restructuring of hydrogen bonding networks. Science Advances 2022, 8: eabm7193. PMID: 35544567, PMCID: PMC9094664, DOI: 10.1126/sciadv.abm7193.
- Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalusDuy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nature Neuroscience 2022, 25: 458-473. PMID: 35379995, PMCID: PMC9664907, DOI: 10.1038/s41593-022-01043-3.
- Protein nanowires with tunable functionality and programmable self-assembly using sequence-controlled synthesisShapiro DM, Mandava G, Yalcin SE, Arranz-Gibert P, Dahl PJ, Shipps C, Gu Y, Srikanth V, Salazar-Morales AI, O’Brien J, Vanderschuren K, Vu D, Batista VS, Malvankar NS, Isaacs FJ. Protein nanowires with tunable functionality and programmable self-assembly using sequence-controlled synthesis. Nature Communications 2022, 13: 829. PMID: 35149672, PMCID: PMC8837800, DOI: 10.1038/s41467-022-28206-x.
- Making protons tag along with electronsGuberman-Pfeffer MJ, Malvankar NS. Making protons tag along with electrons. Biochemical Journal 2021, 478: 4093-4097. PMID: 34871365, DOI: 10.1042/bcj20210592.
- Structure of Geobacter pili reveals secretory rather than nanowire behaviourGu Y, Srikanth V, Salazar-Morales AI, Jain R, O’Brien J, Yi SM, Soni RK, Samatey FA, Yalcin SE, Malvankar NS. Structure of Geobacter pili reveals secretory rather than nanowire behaviour. Nature 2021, 597: 430-434. PMID: 34471289, PMCID: PMC9127704, DOI: 10.1038/s41586-021-03857-w.
- Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formationWong GCL, Antani JD, Lele PP, Chen J, Nan B, Kühn MJ, Persat A, Bru JL, Høyland-Kroghsbo NM, Siryaporn A, Conrad JC, Carrara F, Yawata Y, Stocker R, Brun Y, Whitfield GB, Lee CK, de Anda J, Schmidt WC, Golestanian R, O’Toole G, Floyd KA, Yildiz FH, Yang S, Jin F, Toyofuku M, Eberl L, Nomura N, Zacharoff LA, El-Naggar MY, Yalcin SE, Malvankar NS, Rojas-Andrade MD, Hochbaum AI, Yan J, Stone HA, Wingreen NS, Bassler BL, Wu Y, Xu H, Drescher K, Dunkel J. Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formation. Physical Biology 2021, 18: 10.1088/1478-3975/abdc0e. PMID: 33462162, PMCID: PMC8506656, DOI: 10.1088/1478-3975/abdc0e.
- Intrinsic electronic conductivity of individual atomically resolved amyloid crystals reveals micrometer-long hole hopping via tyrosinesShipps C, Kelly HR, Dahl PJ, Yi SM, Vu D, Boyer D, Glynn C, Sawaya MR, Eisenberg D, Batista VS, Malvankar NS. Intrinsic electronic conductivity of individual atomically resolved amyloid crystals reveals micrometer-long hole hopping via tyrosines. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2014139118. PMID: 33372136, PMCID: PMC7812754, DOI: 10.1073/pnas.2014139118.
- The blind men and the filament: Understanding structures and functions of microbial nanowiresYalcin SE, Malvankar NS. The blind men and the filament: Understanding structures and functions of microbial nanowires. Current Opinion In Chemical Biology 2020, 59: 193-201. PMID: 33070100, PMCID: PMC7736336, DOI: 10.1016/j.cbpa.2020.08.004.
- Electric field stimulates production of highly conductive microbial OmcZ nanowiresYalcin SE, O’Brien J, Gu Y, Reiss K, Yi SM, Jain R, Srikanth V, Dahl PJ, Huynh W, Vu D, Acharya A, Chaudhuri S, Varga T, Batista VS, Malvankar NS. Electric field stimulates production of highly conductive microbial OmcZ nanowires. Nature Chemical Biology 2020, 16: 1136-1142. PMID: 32807967, PMCID: PMC7502555, DOI: 10.1038/s41589-020-0623-9.
- Direct observation of anisotropic growth of water films on minerals driven by defects and surface tensionYalcin SE, Legg BA, Yeşilbaş M, Malvankar NS, Boily JF. Direct observation of anisotropic growth of water films on minerals driven by defects and surface tension. Science Advances 2020, 6: eaaz9708. PMID: 32832658, PMCID: PMC7439304, DOI: 10.1126/sciadv.aaz9708.
- Structure of Microbial Nanowires Reveals Stacked Hemes that Transport Electrons over MicrometersWang F, Gu Y, O’Brien J, Yi SM, Yalcin SE, Srikanth V, Shen C, Vu D, Ing NL, Hochbaum AI, Egelman EH, Malvankar NS. Structure of Microbial Nanowires Reveals Stacked Hemes that Transport Electrons over Micrometers. Cell 2019, 177: 361-369.e10. PMID: 30951668, PMCID: PMC6720112, DOI: 10.1016/j.cell.2019.03.029.
- Expressing the Geobacter metallireducens PilA in Geobacter sulfurreducens Yields Pili with Exceptional ConductivityTan Y, Adhikari RY, Malvankar NS, Ward JE, Woodard TL, Nevin KP, Lovley DR, Beyenal H, Shi L, TerAvest M. Expressing the Geobacter metallireducens PilA in Geobacter sulfurreducens Yields Pili with Exceptional Conductivity. MBio 2017, 8: e02203-16. PMID: 28096491, PMCID: PMC5241403, DOI: 10.1128/mbio.02203-16.
- A Simple and Low‐Cost Procedure for Growing Geobacter sulfurreducens Cell Cultures and Biofilms in Bioelectrochemical SystemsO'Brien JP, Malvankar NS. A Simple and Low‐Cost Procedure for Growing Geobacter sulfurreducens Cell Cultures and Biofilms in Bioelectrochemical Systems. Current Protocols In Microbiology 2016, 43: a.4k.1-a.4k.27. PMID: 27858972, PMCID: PMC5726868, DOI: 10.1002/cpmc.20.
- Reply to 'Measuring conductivity of living Geobacter sulfurreducens biofilms'Malvankar NS, Rotello VM, Tuominen MT, Lovley DR. Reply to 'Measuring conductivity of living Geobacter sulfurreducens biofilms'. Nature Nanotechnology 2016, 11: 913-914. PMID: 27821844, DOI: 10.1038/nnano.2016.191.
- The Low Conductivity of Geobacter uraniireducens Pili Suggests a Diversity of Extracellular Electron Transfer Mechanisms in the Genus GeobacterTan Y, Adhikari RY, Malvankar NS, Ward JE, Nevin KP, Woodard TL, Smith JA, Snoeyenbos-West OL, Franks AE, Tuominen MT, Lovley DR. The Low Conductivity of Geobacter uraniireducens Pili Suggests a Diversity of Extracellular Electron Transfer Mechanisms in the Genus Geobacter. Frontiers In Microbiology 2016, 07: 980. PMID: 27446021, PMCID: PMC4923279, DOI: 10.3389/fmicb.2016.00980.
- Low Energy Atomic Models Suggesting a Pilus Structure that could Account for Electrical Conductivity of Geobacter sulfurreducens PiliXiao K, Malvankar NS, Shu C, Martz E, Lovley DR, Sun X. Low Energy Atomic Models Suggesting a Pilus Structure that could Account for Electrical Conductivity of Geobacter sulfurreducens Pili. Scientific Reports 2016, 6: 23385. PMID: 27001169, PMCID: PMC4802205, DOI: 10.1038/srep23385.
- Conductivity of individual Geobacter piliAdhikari R, Malvankar N, Tuominen M, Lovley D. Conductivity of individual Geobacter pili. RSC Advances 2016, 6: 8354-8357. DOI: 10.1039/c5ra28092c.
- Electronic Conductivity in Living Biofilms: Physical Meaning, Mechanisms, and Measurement MethodsMalvankar N, Lovley D. Electronic Conductivity in Living Biofilms: Physical Meaning, Mechanisms, and Measurement Methods. 2015, 211-248. DOI: 10.1002/9781119097426.ch7.
- Functional environmental proteomics: elucidating the role of a c-type cytochrome abundant during uranium bioremediationYun J, Malvankar NS, Ueki T, Lovley DR. Functional environmental proteomics: elucidating the role of a c-type cytochrome abundant during uranium bioremediation. The ISME Journal: Multidisciplinary Journal Of Microbial Ecology 2015, 10: 310-320. PMID: 26140532, PMCID: PMC4737924, DOI: 10.1038/ismej.2015.113.
- Impedance Spectroscopy of Ionic Ligand‐Modulated Charge Transport of Gold Nanoparticle FilmsYu X, Malvankar N, Landis R, Eymur S, Miranda OR, Rotello VM. Impedance Spectroscopy of Ionic Ligand‐Modulated Charge Transport of Gold Nanoparticle Films. Small 2015, 11: 3814-3821. PMID: 25919594, DOI: 10.1002/smll.201500127.
- Aromatic Amino Acids Required for Pili Conductivity and Long-Range Extracellular Electron Transport in Geobacter sulfurreducensVargas M, Malvankar N, Tremblay P, Leang C, Smith J, Patel P, Snoeyenbos-West O, Nevin K, Lovley D. Aromatic Amino Acids Required for Pili Conductivity and Long-Range Extracellular Electron Transport in Geobacter sulfurreducens. MBio 2013, 4: e00210-13. PMCID: PMC3622933, DOI: 10.1128/mbio.00210-13.
- Engineering Geobacter sulfurreducens to produce a highly cohesive conductive matrix with enhanced capacity for current productionLeang C, Malvankar N, Franks A, Nevin K, Lovley D. Engineering Geobacter sulfurreducens to produce a highly cohesive conductive matrix with enhanced capacity for current production. Energy & Environmental Science 2013, 6: 1901-1908. DOI: 10.1039/c3ee40441b.
- Cover Picture: Supercapacitors Based on c‐Type Cytochromes Using Conductive Nanostructured Networks of Living Bacteria (ChemPhysChem 2/2012)Malvankar N, Mester T, Tuominen M, Lovley D. Cover Picture: Supercapacitors Based on c‐Type Cytochromes Using Conductive Nanostructured Networks of Living Bacteria (ChemPhysChem 2/2012). ChemPhysChem 2012, 13: 365-365. DOI: 10.1002/cphc.201290005.
- Promoting direct interspecies electron transfer with activated carbonLiu F, Rotaru A, Shrestha P, Malvankar N, Nevin K, Lovley D. Promoting direct interspecies electron transfer with activated carbon. Energy & Environmental Science 2012, 5: 8982-8989. DOI: 10.1039/c2ee22459c.
- Comment on “On electrical conductivity of microbial nanowires and biofilms” by S. M. Strycharz-Glaven, R. M. Snider, A. Guiseppi-Elie and L. M. Tender, Energy Environ. Sci. , 2011, 4 , 4366Malvankar N, Tuominen M, Lovley D. Comment on “On electrical conductivity of microbial nanowires and biofilms” by S. M. Strycharz-Glaven, R. M. Snider, A. Guiseppi-Elie and L. M. Tender, Energy Environ. Sci. , 2011, 4 , 4366. Energy & Environmental Science 2012, 5: 6247-6249. DOI: 10.1039/c2ee02613a.
- Biofilm conductivity is a decisive variable for high-current-density Geobacter sulfurreducens microbial fuel cellsMalvankar N, Tuominen M, Lovley D. Biofilm conductivity is a decisive variable for high-current-density Geobacter sulfurreducens microbial fuel cells. Energy & Environmental Science 2012, 5: 5790-5797. DOI: 10.1039/c2ee03388g.
- Lack of cytochrome involvement in long-range electron transport through conductive biofilms and nanowires of Geobacter sulfurreducensMalvankar N, Tuominen M, Lovley D. Lack of cytochrome involvement in long-range electron transport through conductive biofilms and nanowires of Geobacter sulfurreducens. Energy & Environmental Science 2012, 5: 8651-8659. DOI: 10.1039/c2ee22330a.
- Bacterial biofilms: the powerhouse of a microbial fuel cellFranks A, Malvankar N, Nevin K. Bacterial biofilms: the powerhouse of a microbial fuel cell. Biofuels 2010, 1: 589-604. DOI: 10.4155/bfs.10.25.